Gene Therapy Research Unit (GTRU), Children's Medical Research Institute
Lab head: Dr Ian Alexander
Location: Children's Medical Research Institute, Westmead
We are working on developing new therapies for the treatment of genetic and acquired diseases of the liver and haematopoietic system.
Lab members: Prof Ian E Alexander (Head)
Funding: NHMRC; ARC; UK MRC
Research approach equipment: Since its inception in 1995, the unit has systematically established the resources and infrastructure to make fundamental discoveries in basic science and translate the findings via preclinical models from laboratory bench to patient bedside. The research is always guided by a 'ground-up' approach to realise the long-term vision to implement gene therapies in the clinic.
Repairing genetic mutations in the liver stem cell using recombinant adeno-associated virus (AAV)
Primary supervisor: Ian Alexander
Gene therapy is beginning to fulfil its potential in the clinic for the treatment of monogenic disorders. All reports to date rely on a “gene addition” approach such that diseased cells are modified to encode the correct copy of an affected gene. The ideal strategy , however, is “gene repair” so that gene expression is maintained under endogenous regulatory elements. In this respect, AAV-mediated homologous recombination (HR) demonstrates 1000-fold greater efficiencies for gene repair over alternative approaches that use plasmid DNA and adenovirus. Despite the greater efficiencies mediated by AAV gene repair, the system requires further improvement to provide therapeutic utility.
The aim of this project is to optimise AAV mediated homologous recombination to repair mutant loci in liver stem cells (LPC), a cell type with therapeutic potential to treat metabolic liver disease. LPC can be propagated and expanded ex vivo whilst retaining the ability to terminally differentiate into hepatocytes for engraftment in the diseased liver. Our laboratory has made considerable progress with this project which offers experience in a range of laboratory techniques including molecular biology, packaging of recombinant viruses, tissue culture, histology and animal studies.
Co-supervisors: Grant Logan
Keywords: Gene therapy, Stem cells, Liver